Field of the Invention
The present invention relates to compositions which comprise a cardiac glycoside or cardiac glycosides for use in the treatment and prevention of hair loss conditions and disorders.
Description of the Prior Art
Hair loss is an extremely prevalent condition and it is estimated that approximately 20 to 25% of the population suffer from some type of hair loss disorder. Whilst hair loss is more common in adult males, hair loss disorders also affect women and children. Although most hair loss disorders are not in themselves damaging to the health of an individual, many sufferers report associated psychological problems including anxiety and depression.
However, despite the prevalence of hair loss disorders, few efficacious treatments are available. Surgical treatments are available for the restoration of hair, particularly to the scalp. However, these techniques are painful, expensive, and suffer from the inherent dangers associated with any invasive surgery. Furthermore, hair restoration surgeries typically require at least some areas of dense hair growth to be available on the patient for transplant or relocation to other areas of the body. Yet further, surgical treatments are rarely applicable to sufferers of alopecia areata in which spontaneous regrowth of hair which subsequently falls out again, often occurs.
Hair loss compositions are thus an attractive proposition for those suffering from hair loss conditions. A range of therapies are available for which partial success in the treatment of alopecia has been claimed. The various therapies available can be divided up into several groups comprising non-specific immunosuppressants such as corticosteroids or UVA treatment, contact dermatitis inducers, specific immunosuppressants such as cyclosporins, non-specific irritants and other treatments such as alternative and experimental therapies.
Non specific immunosuppressants such as corticosteroids function by mimicking the steroidal hormones produced by the adrenal glands to suppress inflammation. Corticosteroids can be administered topically to the affected area, through intralesional injections, or systemically via injection or oral medication, depending on the severity of the condition. While topical corticosteroids are commonly used to treat alopecia areata, there is little evidence that they promote hair regrowth. Intralesional administration of corticosteroids has demonstrated more efficacy in the treatment of alopecia areata, with a study reported by Porter and Burton (Br. J. Dermatol. 1971:85, 272-273) demonstrating that hair regrowth was achieved in 33 out of 34 sites injected with triamcinolone hexacetonide in 11 patients and in 16 out of 25 sites injected with triamcinolone acetonide in 17 patients, with the affects lasting about nine months. However, intralesional corticosteroid administration is most suitable for treating patchy hair loss of limited extent and for cosmetically sensitive sites such as the eyebrows, with skin atrophy at the site of injection a consistent side-effect. Systemic corticosteroid administration has achieved some hair regrowth in alopecia suffers. However, studies have demonstrated only 30-47% of patients showed significant hair regrowth and thus in most patients the response achieved is insufficient to justify the risks associated with prolonged treatment.
A combination of UVA actinotherapy with 8-methoxypsoralen (an irritant and immuno-modulator) has also been utilised for the treatment of alopecia. However, this method of treatment, commonly called PUVA, is not popular due to the frequency of treatment required, potentially dangerous side-effects and low success rates. Furthermore, the relapse rate following treatment is high and continued treatment is usually required which may lead to high cumulative UVA dosages.
Contact dermatitis inducers work by sensitising the immune system. A low level of the drug is initially applied and adjusted until a reaction is established. Contact dermatitis inducers utilised for the treatment of alopecia areata include dinitrochlorobenzene (DNCB), diphenylcyclopropenone (DPCP) and squaric-acid-dibutylester (SADBE). Reviews of these treatments have concluded that the range of response rates is wide, at reportedly 9 to 87% (Rokhsar et al. J Am Acad Dermatol 1998:39:751-761). Side affects including severe dermatitis and occipital and/or cervical lymphadenopathy are often common.
Specific immunosuppressants for the treatment of alopecia include cyclosporins and tacrolimus (FK506). These drugs act by inhibiting T-cell activation. While results have demonstrated some efficacy for cyclosporins, side-effects are a major consideration and results may often not justify the associated risks.
Non-specific irritants function by interrupting cell differentiation in the skin with the damage caused stimulating immune cell activity. Irritants that have been employed for the treatment of alopecia areata include anthralin, iodine, chrysarobin, croton oil, capsicum and dithranol. However, results in studies on anthralin indicate low levels of efficacy with one open study demonstrating significant regrowth in just 18% of patients. Furthermore, staining of hair limits the use of anthralin in fair-haired patients.
Alternative treatments such as essential oils and acupuncture and experimental and theoretical treatments such as cytokines, biologicals, desensitisation, oral tolerance and gene therapy have been variously employed in the treatment of alopecia with varying degrees of success.
Recent research has indicated that a technique called follicular cell implantation, in which dermal papilla cells are taken from the patient, multiplied in a laboratory and then injected into the affected area, may be effective in the treatment of hair loss disorders with 11 out of 19 patients reporting hair regrowth. However, this technique is at an early stage of development and results thus far are based on a very small number of patients, making the efficacy of this treatment difficult to assess.
All hair loss treatments currently known require long-term regular use to maintain any efficacious effects achieved. Of the above treatments, many require administration by a health care professional and involve potentially dangerous side-effects. Currently few hair loss compositions which can be self-administered have demonstrated clinical efficacy in the treatment or prevention of hair loss. Minoxidil, or 3-hydroxy-2-imino-6-(1-piperidyl)pyrimidin-4-amine is a vasodilatory medication that was discovered to have the side-effect of promoting hair growth when used to treat high blood pressure. The mechanism by which minoxidil promotes hair growth is not well understood, although it has been postulated that it may be due to an increase in blood supply to the hair follicles. Whilst minoxidil has demonstrated some efficacy in promoting hair growth, it is considered to be effective in less than 60% of patients, with there currently being no indication as to which patients are most likely to respond.
Finasteride has also demonstrated some efficacy in treating hair loss. Finasteride is a 5α-reductase inhibitor, which functions by blocking the conversion of testosterone to the active 5α-dihydrotesterone (DHT) form, elevated levels of which have been linked to hair loss. Studies indicate effectiveness in approximately 50% of patients, with side effects including erectile dysfunction and gynecomastica being reported. Furthermore finasteride is not indicated for use in women of childbearing age as it can cause birth defects in unborn babies.
Oxalates have also been reported to demonstrate efficacy in the treatment of hair loss disorders. International Patent Application No. WO 94/15574 discloses that oxalates of group Ia or IIa metals could be used for preventing hair loss and stimulating growth and Canadian patent No. 888689 discloses the use of a composition for the treatment of the scalp against hair loss which requires the use of an emulsion containing bergamot oil, water and a ferrous salt including a ferrous oxalate (i.e. a group VIII metal salt). However, oxalates such as calcium oxalate as described in the prior art appear as crystals which can pierce and intensely irritate the skin, making oxalates unsuitable for some patients.